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Indian Journal of Endocrinology and... 2023In this study, it was aimed to examine the clinical and laboratory findings that can be used to predict central precocious puberty (CPP) in cases whose breast...
AIM
In this study, it was aimed to examine the clinical and laboratory findings that can be used to predict central precocious puberty (CPP) in cases whose breast development started before the age of 8.
MATERIALS AND METHODS
The chronological age, anthropometric measurements, bone age (BA), hormone test results and pelvic ultrasonography findings of the cases were recorded. Those with a peak luteinizing hormone (LH) level of ≥5 IU/L in the gonadotropin-releasing hormone (GnRH) stimulation test were classified as CPP and those with a peak LH level of <5 IU/L were classified as prepubertal cases. A receiver operating characteristic (ROC) analysis was performed to determine the diagnostic accuracy of laboratory variables.
FINDINGS
A total of 297 female cases were included in the study. The age at the time of admission, height-standard deviation score (SDS), BA, the long axis of the uterus and the volumes of the right and left ovaries of the cases diagnosed with CPP were found to be significantly higher than those of the prepubertal group. The cut-off value providing the best sensitivity (99%) and specificity (99%) for the peak LH was found to be 4.55; the cut-off value providing the best sensitivity (94%) and specificity (85%) for the peak LH/follicle-stimulating hormone (FSH) ratio was found to be 0.32 and the cut-off value providing the best sensitivity (47%) and specificity (93%) for the basal LH was found to be 0.13.
CONCLUSION
We believe that in female cases with early breast development, a peak LH level of ≥4.55 may possibly indicate CPP and a basal LH level of <0.13 can significantly rule out CPP.
PubMed: 37583412
DOI: 10.4103/ijem.ijem_245_22 -
The Neuroradiology Journal Jun 2024Pituitary gland duplication is a rare abnormality and isolated duplication of the pituitary stalk without any pituitary anomaly is an even rarer entity with this case... (Review)
Review
Pituitary gland duplication is a rare abnormality and isolated duplication of the pituitary stalk without any pituitary anomaly is an even rarer entity with this case being the first documented case till date. Although incidentally discovered cases of duplication of pituitary gland (DPG) have been reported, sometimes with a duplicated pituitary stalk, patients with this disorder usually present with other craniofacial abnormalities. Consequently, DPG plus syndrome is used as it is often accompanied by endocrine disturbances and pathologies such as median cleft face syndrome, ocular disorders, craniocervical bony abnormalities, vascular anomalies and tuberomammillary masses. Since this is the first reported case without any additional pituitary gland anomaly, we propose the acronym DPS (duplication of pituitary stalk) to be used to unify this entity as we are certain that much like the previously described pituitary duplication disorders, more cases will be documented independently rather than under the umbrella of pituitary duplication disorders. This is critical as the life expectancy (age of diagnosis) in the cases reviewed in our study is as good as normal population with no obvious increase in mortality as compared to existing pituitary duplication syndromes. We present a case report of a 2 year 7 month old girl who was referred by the paediatrician for evaluation of premature thelarche. The duplication of the pituitary stalk along with mega cisterna magna and tuberomammillary fusion was the only positive finding on imaging with the pituitary gland being absolutely normal.
Topics: Humans; Female; Pituitary Gland; Child, Preschool; Magnetic Resonance Imaging; Pituitary Diseases
PubMed: 37507120
DOI: 10.1177/19714009231193157 -
Current Pediatric Reviews Jul 2023Premature thelarche is the most common pubertal disorder in girls. The condition should be differentiated from central precocious puberty which may result in early...
BACKGROUND
Premature thelarche is the most common pubertal disorder in girls. The condition should be differentiated from central precocious puberty which may result in early epiphyseal fusion and reduced adult height, necessitating treatment.
OBJECTIVE
The purpose of this article is to familiarize physicians with the clinical manifestations of premature thelarche and the clinical features and laboratory tests that may help distinguish premature thelarche from central precocious puberty.
METHODS
A search was conducted in September 2022 in PubMed Clinical Queries using the key term " Premature thelarche". The search strategy included all clinical trials, observational studies, and reviews published within the past 10 years. Only papers published in the English literature were included in this review. The information retrieved from the above search was used to compile the present article.
RESULTS
Premature thelarche denotes isolated breast development before the age of 8 years in girls who do not manifest other signs of pubertal development. The condition is especially prevalent during the first two years of life. The majority of cases of premature thelarche are idiopathic. The condition may result from an unsuppressed hypothalamic-pituitary-gonadal axis in the early years of life, an "overactivation" of the hypothalamic-pituitary axis in early childhood secondary to altered sensitivity to steroids of the hypothalamic receptors controlling sexual maturation, increased circulating free estradiol, increased sensitivity of breast tissue to estrogens, and exposure to exogenous estrogens. The cardinal feature of premature thelarche is breast development which occurs without additional signs of pubertal development in girls under 8 years of age. The enlargement may involve only one breast, both breasts asymmetrically, or both breasts symmetrically. The breast size may fluctuate cyclically. The enlarged breast tissue may be transiently tender. There should be no significant changes in the nipples or areolae and no pubic or axillary hair. The vulva, labia majora, labia minora, and vagina remain prepubertal. Affected girls have a childlike body habitus and do not have mature contours. They are of average height and weight. Growth and osseous maturation, the onset of puberty and menarche, and the pattern of adolescent sexual development remain normal. Most cases of premature thelarche can be diagnosed on clinical grounds. Laboratory tests are seldom indicated. No single test can reliably differentiate premature thelarche from precocious puberty.
CONCLUSION
Premature thelarche is benign, and no therapy is necessary apart from parental reassurance. As enlargement of breasts may be the first sign of central precocious puberty, a prolonged follow-up period every 3 to 6 months with close monitoring of other pubertal events and linear growth is indicated in all instances.
PubMed: 37496240
DOI: 10.2174/1573396320666230726110658 -
Early Human Development Aug 2023A secular trend towards earlier age at menarche has been reported, but the trend in breast development is less clear. We reviewed the evidence on the relationship... (Review)
Review
BACKGROUND
A secular trend towards earlier age at menarche has been reported, but the trend in breast development is less clear. We reviewed the evidence on the relationship between in utero and early life events and breast onset/development.
METHODS
Eligible studies were identified in PubMed and Embase databases. We selected studies in which female human exposure during fetal or the first years of life was measured or estimated, and associations with breast onset or development were evaluated.
RESULTS
Of the 49 cohort studies and 5 cross-sectional studies identified, 43 provided sufficient data to assess associations. High maternal weight, primiparity, and early weight gain, were related to an increased risk of early breast onset/development in most of the studies that analysed these associations, whereas late breast onset/development was associated with preterm birth. Results were inconsistent for smoking in pregnancy, maternal hypertensive disorders, breastfeeding, diabetes, and small for gestational age. No association emerged for maternal age at delivery, alcohol drinking, and selected drug use during pregnancy, and low birth weight.
CONCLUSIONS
The results of this review show that high maternal weight, primiparity and early weight gain were associated with an increased risk of early breast onset/development. Late breast onset/development was associated with preterm birth. Breast development is a key physical marker of puberty onset, and early puberty development is linked to consequences that can reverberate throughout life. Answering the questions about the interconnections between pre/postnatal environmental exposures and their impact on puberty, represents an important area of multidisciplinary research.
Topics: Pregnancy; Infant, Newborn; Female; Humans; Premature Birth; Cross-Sectional Studies; Prenatal Care; Maternal Age; Weight Gain
PubMed: 37421688
DOI: 10.1016/j.earlhumdev.2023.105816 -
Annals of Pediatric Endocrinology &... Jun 2023Intravenous gonadotropin-releasing hormone (IV GnRH) testing is the gold standard for confirming a central precocious puberty (CPP) diagnosis. However, this test is not...
The utilization of basal luteinizing hormone in combination with the basal luteinizing hormone and follicle-stimulating hormone ratio as a diagnostic tool for central precocious puberty in girls.
PURPOSE
Intravenous gonadotropin-releasing hormone (IV GnRH) testing is the gold standard for confirming a central precocious puberty (CPP) diagnosis. However, this test is not widely available commercially. Therefore, our study aim was to establish cutoff values for basal gonadotropin level and gonadotrophin responses to a 100-μg subcutaneous IV GnRH test that can distinguish between CPP and premature thelarche (PT) to discover a simple method to detect CPP.
METHODS
Girls between the ages of 6 and 8 years who attended the pediatric endocrinology outpatient clinic at our tertiary hospital between 2019 and 2022 were included in this study. They were evaluated for breast development, and a subcutaneous 100-μg GnRH test was administered by measuring the luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels in blood samples at baseline and then 30, 60, 90, and 120 minutes after injection. CPP is characterized by increased height velocity, advanced bone age, and progression of breast development. The cutoff value for diagnosis of CPP was determined using a receiver operating characteristic (ROC) analysis.
RESULTS
In 86 Thai girls (56 with CPP and 30 with PT), the ROC analysis showed 71.4% and 100% sensitivity and specificity, respectively, for basal LH (cutoff ≥ 0.2 IU/L) plus the basal LH/FSH ratio (cutoff ≥ 0.1). The optimal cutoff values for peak LH (cutoff ≥ 7 IU/L) demonstrated a sensitivity of 94.6% and a specificity of 100%, whereas the LH value at 30 and 60 minutes after injection (cutoff ≥ 6 IU/L) demonstrated sensitivities of 92.9% and 94.6% and a specificity of 100%, respectively.
CONCLUSION
Combining the basal LH (cutoff: 0.2 IU/L) and the basal LH/FSH ratio (cutoff: 0.1) can easily and cost-effectively diagnose CPP in a girl in breast Tanner stage II.
PubMed: 37401058
DOI: 10.6065/apem.2346072.036 -
Annales D'endocrinologie Feb 2024Aromatase deficiency is a rare disorder, with only a few cases reported in India. We describe a single-center experience in western India, with a systematic review of...
BACKGROUND
Aromatase deficiency is a rare disorder, with only a few cases reported in India. We describe a single-center experience in western India, with a systematic review of genetically proven 46,XX aromatase deficiency patients to evaluate hormonal parameters.
METHODS
Retrospective review of case records, collating phenotypic and genotypic data and molecular modeling. Systematic review of 46,XX aromatase deficiency, analyzing data on gonadotropins, estrogen and androgens.
RESULTS
In the seven patients from our center, presentation was frequent in childhood or adolescence (4/7: delayed puberty or hyperandrogenism), with maternal virilization (4/7), predominance of Prader III/IV (5/7), and initial rearing as females (6/7). Three patients had hypoplastic ovaries. One patient had spontaneous regular menses. We report three novel (p.Arg115Pro, p.Arg192Pro, and c.145+1_145+4delins) and two recurrent variants (p.Val370Met, and c.145+1_145+4delins) in western and northern India, respectively. On systematic review (n=43), gonadotropins were elevated (FSH>LH) across ages (except preterm infants), androgens were elevated in about one-third of cases during childhood and puberty, and estradiol was lower than in controls in mini-puberty and puberty. Spontaneous thelarche and streak ovaries were significantly more frequent in patients with non-truncating and truncating variants, respectively.
CONCLUSION
We report uncommon presentations with possible founder variants, and highlight hormonal parameters across ages. Serum FSH levels were elevated except in preterms, and can be used as a diagnostic marker.
Topics: Male; Infant; Female; Adolescent; Humans; Infant, Newborn; Infant, Premature; Gynecomastia; Androgens; Follicle Stimulating Hormone; Gonadotropins; Aromatase; Infertility, Male; Metabolism, Inborn Errors; 46, XX Disorders of Sex Development
PubMed: 37348676
DOI: 10.1016/j.ando.2023.05.010 -
Journal of Clinical Research in... Aug 2023
Topics: Male; Child; Female; Humans; Animals; Rats; Gynecomastia; Puberty, Precocious; Propolis; Breast; Gonadotropin-Releasing Hormone
PubMed: 37338296
DOI: 10.4274/jcrpe.galenos.2023.2023-5-9 -
Indian Pediatrics Jun 2023To describe the characteristics of gonadotropin-dependent precocious puberty (GDPP) in Indian children.
OBJECTIVE
To describe the characteristics of gonadotropin-dependent precocious puberty (GDPP) in Indian children.
METHODS
Clinical profiles of GDPP (n=78, 61 females) and premature thelarche (n=12) from a single center in Western India were retrospectively studied.
RESULTS
Pubertal onset was earlier in boys than girls (29 vs 75 months, respec-tively; P=0.008). The basal luteinizing hormone (LH) was ≥0.3 mIU/mL, except 18% of GDPP girls. At 60 minutes after GnRHa-stimulation, all patients (except one girl) had LH ≥5 mIU/mL. The GnRHa-stimulated LH/FSH ratio was ≥0.34 at 60 minutes in girls with GDPP unlike premature thelarche. Only one girl had an allergic reaction to long-acting GnRH agonist. Among GnRH agonist-treated girls (n=24), the predicted final adult height was -1.67±1.5 SDS, whereas the attained final height was -0.25±1.48 SDS.
CONCLUSION
We establish the safety and efficacy of long acting GnRH agonist therapy in Indian children with GDPP. The 60-minute stimulated serum LH/FSH of ≥0.34 differentiated GDPP from premature thelarche.
Topics: Child; Female; Male; Adult; Humans; Puberty, Precocious; Gonadotropin-Releasing Hormone; Follicle Stimulating Hormone; Retrospective Studies; Luteinizing Hormone; Puberty
PubMed: 37211886
DOI: No ID Found -
BMC Pediatrics Apr 2023To investigate the differential diagnosis of girls aged 6 to 8 years with idiopathic premature thelarche (IPT) and central precocious puberty (CPP) during the COVID-19...
BACKGROUND
To investigate the differential diagnosis of girls aged 6 to 8 years with idiopathic premature thelarche (IPT) and central precocious puberty (CPP) during the COVID-19 pandemic. We explored predicted adult height (PAH) discrepancy to guide appropriate diagnosis and treatment.
METHODS
From January 2020 to December 2021, Chinese girls aged 6 to 8 years with precocious puberty were recruited. They were divided into IPT and CPP groups. Clinical characteristics, including height, weight, body mass index (BMI), basal luteinizing hormone (LH), oestradiol, uterine length and volume, follicle numbers (d > 4 mm) and bone age (BA) were recorded. We analysed differential diagnosis and PAH discrepancy in both groups. Binary logistic regression analysis was used to explore risk factors for CPP, and receiver operating characteristic (ROC) curves were generated to evaluate the diagnostic value of related indexes.
RESULTS
Sixty patients, including 40 girls with IPT and 20 girls with CPP, were recruited. The prevalence of overweight and obesity in the entire cohort was 25% (15/60) and was significantly higher in IPT than CPP, 32.5% (13/40) vs. 10% (2/20), respectively (P=0.045). There were significant differences in LH, uterine volume, follicle numbers and BA (P<0.05). The impaired PAH of IPT and CPP was 0.01 ± 1.19 SD and 0.62 ± 0.94 SD with significant differences (P=0.047). Logistic regression analysis showed that LH and follicle numbers were independent risk factors for CPP. The ROC curve showed that the area under the curve (AUC) of LH and follicle numbers were 0.823 and 0.697. The sensitivity and specificity of LH with a cut off of 0.285 IU/L were 78.9% and 77.8%. The sensitivity and specificity of follicle numbers with a cut off of 3.5 were 89.5% and 52.8%.
CONCLUSION
The prevalence of overweight and obesity in 6- to 8-year-old girls with precocious puberty was high. Auxological data should not be used in the differential diagnosis of IPT and CPP. Basal LH above 0.285 IU/L and follicle numbers greater than 4 were important features suggestive of CPP. PAH was impaired in individuals with CPP, but it was not impaired in individuals with IPT.
Topics: Female; Adult; Humans; Child; Puberty, Precocious; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Pilot Projects; Overweight; Diagnosis, Differential; Pandemics; COVID-19; Luteinizing Hormone; Obesity; COVID-19 Testing
PubMed: 37081435
DOI: 10.1186/s12887-023-04009-x -
Scientific Reports Apr 2023Phthalate esters (PAEs) may act as estrogen receptor agonists, and their relationship with precocious puberty is a global health concern. However, their role in isolated...
Phthalate esters (PAEs) may act as estrogen receptor agonists, and their relationship with precocious puberty is a global health concern. However, their role in isolated premature thelarche (IPT) progression remains unclear. We conducted a cohort study investigating the relationship between IPT progression and urinary PAE metabolites. Girls with IPT aged 6-8 years were regularly followed up every three months for one year. Clinical data and urine PAE metabolite levels were collected. Participants who progressed to central precocious puberty (CPP) or early puberty (EP) had significantly higher ovarian volume, breast Tanner stage, and levels of the creatinine-adjusted urinary secondary oxidized di-2-ethylhexyl phthalate (DEHP) metabolites (ΣDEHP). Breast Tanner stage (odds ratio [OR] = 7.041, p = 0.010), ovarian volume (OR = 3.603, p = 0.019), and ΣDEHP (OR = 1.020, p = 0.005) were independent risk factors for IPT progression. For each 10 µg/g/Cr increase in the urine level of ΣDEHP, the risk of progression from IPT to CPP/EP within one year increased by 20%. This study demonstrated that the breast Tanner stage, ovarian volume, and ΣDEHP in urine were independent risk factors for IPT progression, and ΣDEHP may be associated with the progression of IPT to CPP or EP.
Topics: Female; Humans; Puberty, Precocious; Diethylhexyl Phthalate; Cohort Studies; Puberty
PubMed: 37019965
DOI: 10.1038/s41598-023-32768-1